The middle latency response (MLR) can be used as a measure of low frequency hearing, a neurologic measure of function of the higher levels of the auditory pathway and an objective index of cochlear implant function. Clinical use of the MLR is currently limited by inadequate understanding of 1) the underlying generator sites, 2) MLR development, and 3) the extent to which the auditory brainstem response (ABR) and MLR can be used to predict low frequency hearing loss in adult and developing subjects. The aims of this grant are: (1) To determine specific generator sites of the MLR in an aminal model using intracranial mapping, neural inactivation techniques and histologic reconstruction. It is expected that these procedures will also further the understanding of inhibitory mechanisms thought to modulate the MLR. (2) To investigate maturational changes in the MLR. In humans, the MLR develops throughout the first decade of life. By using gerbils, the difficulty of adequately sampling a human population over 10 years can be circumvented. The gerbil auditory system develops completely within a few months. To be investigated are developmental changes in spectral content of the EEG and MLR and the use of ABR and MLR to predict low frequency hearing in developing animals. It has been speculated that low frequency noise in the EEG obscures the MLR in children. This work is expected to lead to an optimal MLR recording strategy for use with children. (3) To examine the use of ABR and MLR in the assessment of low frequency hearing in animals with high frequency (noise-induced) hearing loss. The relationship between electrophysiologic measures (ABR and MLR) and the configuration of the hearing loss, as determined by compound action potential (AP) thresholds will be investigated and described mathematically. It is expected that resulting equations can be used clinicallly to predict the behavioral audiogram based on elelctrophysiological measures. Studies will be initiated in adult animals and will continue with developing subjects. A similar approach is problematic in humans because of the difficulty of obtaining complete behavioral and electrophysiologic data in a single test session and the obvious limitations of behavioral testing in children. Aims 2 and 3 are designed so that data on experimental animals will be comparable to ongoing human studies in our laboratory.